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Can We Preserve The Bladder In Muscle Invasive Bladder Cancer? Dr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon Westmead Hospital University.

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Presentation on theme: "Can We Preserve The Bladder In Muscle Invasive Bladder Cancer? Dr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon Westmead Hospital University."— Presentation transcript:

1 Can We Preserve The Bladder In Muscle Invasive Bladder Cancer? Dr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon Westmead Hospital University of Sydney

2 The Outcomes of Radical Cystectomy Outcomes of RC are very good. Recurrences occur: Median 12 months 86% of recurrences occur in first 3 years. Local only recurrence more likley in OC. Most series- any recurrence= death. Even with LN+ve disease, 30% likelihood of long term survival. Stein Journal of Clinical Oncology, Vol 19, No 3 (February 1), 2001: pp

3 Upstaging is common with Bladder Cancer Based on TURBT, EUA, CT –MRI with dynamic contrast enhancement and Fe particles may be better. –Ureteric obstruction- 67%-90% >pT2 (Skinner et,al,1998) Muscle invasive bladder cancer (cT2) is upstaged to pT3 in: –52% (Soloway –78% (Pagano –41% (Frazier Most cT2 bladder cancers are pT3 or higher. Occult LN mets increase with increasing P stage –P0, Pa, Pis, P1:5% –P2:18-27% –P3-4:45%

4 Quality of Life After RC is Good. There are a number of QoL instruments for bladder cancer. Very few reports on QoL after BC treatment. Lack of baseline measurements. Lack of longitudinal measurements. No comparison of RC vs Bladder Preservation. Only on prospective QoL study (SF-36) (Hardt Physical functioning decreased pre-post-op (80 to 68) Pain, health perception, vitality, social functioning, general well being, satisfaction with life all the same as pre-op at one year.

5 Options of Bladder Preservation with Muscle Invasive BC TURBT alone Partial Cystectomy alone External Beam Radiation Alone Brachytherapy Neoadjuvant Chemo and TURBT Neoadjuvant Chemo and Partial cystectomy Multimodality therapy

6 Does a delay in cystectomy Result in lower survival? Randomised studies of immediate cystectomy vs XRT and salvage cystectomy. StudyRandomised groupsSurvival MD Andersen (n=67) Immediate XRT+cystectomy5yrs: 45% XRT and salvage cystectomy5yrs: 22% Urologic Co- operative Group UK (n=187) Immediate cystectomy5 yrs: 39% XRT with salvage surgery5 yrs: 29% Danish National Bladder Group (n=187) Immediate XRT+cystectomy5 yrs: 29% XRT and salvage cystectomy5 yrs: 23% Possibly: Need low threshold for salvage cystectomy

7 TURBT TURBT is feasible for selected T2 bladder tumours.TURBT is feasible for selected T2 bladder tumours. Not for dome or high posterior wall AuthorProtocolSurvivalCystectomy rate Barnes (n=85)G1/2 T2 TURBT X1 27% 5 yrs Henry (n=43)Favourable (small T2) TURBT X1 77% 5 yrs25% Solsona (n=59)Negative cytology and rpt biopsy yrs19% Herr (n=45)Negative rpt TUR and cytology 5 yrs24%

8 Partial Cystectomy MSKCC study (contemporary) 85 patients with T2 OS: 5yrs 74% alive with bladder intact 67% alive with NED bladder intact 7 pts sup recurrence 15 pts advanced recurrence –75% false negative frozen section margins. –80% of positive margins suffered advanced recurrence. Selection: Dome/post wall/diverticulum

9 Partial Cystectomy Candidates: –CR or PR to Neoadjuvant chemo –Solitary lesions in favoyrable locations –No CIS –Good bladder capacity.

10 Radiation StudyPatient no.Survival (5 yr%) T2T3 Fossa Davidson Gospodarowicz Goffinet TURBT and 65 Gy XRT Tumour debulking (TURBT may be most important) Assessment of response at 40Gy may be useful CR to XRT- will have a good outcome. 60% invasive recurrence rate. Approx 50% cystectomy rate. Co-existant CIS: High recurrence rate in bladder (70%). Squamous differentiation may have poorer outcome

11 Radiation-Complications Early complications Diarrhea Bladder irritation (particularly if trigonal cancers) Late complications (2-3 years later) Worse if heavily pretreated (TURBTS, BCG etc) Radiation cystitis (heamturia, frequency contracted bladder) Radiation proctitis (persistent diarrhea, rectal bleeding) Sexual dysfunction (60%) Tumour Recurrence Invasive – salvage cystectomy Superficial- as per normal protocols

12 Neoadjuvant and Partial cystectomy Neoadjuvant chemotherapy (X3-4 cycles) followed by TURBT staging. Then followed by partial cystectomy and pelvic lymph node dissection. Herr (n=26). No Pt was eligible for PC alone. –19 had P0 –7 yr median FU:65% alive 54% with bladder 18% invasive recurrence 26% superficial recurrence PC is a valid option in suitable patients, even with T3 tumours that are small.

13 Neoadjuvant and TURBT Neoadjuvant chemo (3-4 cycles). Restaging TURBT. Stenberg (n=71). T2-T4a –Median 54 months FU:71% alive 57% bladder intact After chemo: P0 or superficial disease, 5yr survival = 71% Invasive disease29% MSKCC (n=111) 60(54%) achieved T0 status.- Most preserved bladders 56% recurrence in bladder (30% invasive) 25% of T0 is not P0.

14 Neoadjuvant chemotherapy and TURBT Srougi (n=30) TURBT, MVACX3. –PR or no response > cystectomy (n=12) –CR > all retained their bladder (n=14) 5 yrs, 71% (10) had local recurrences. –8 had radical cystectomy Survival of all CR pts was 5yrs. All patients need close observation because of inadequate staging and occurrence of new tumours.All patients need close observation because of inadequate staging and occurrence of new tumours.

15 Trimodality Therapy Maximal TURBT XRT Concurrent chemotherapy Rational –Cisplatin, 5-FU and paclitaxel sensitise tumour tissues to XRT. –Increase cell kill in a synergisitic fashion. –Also high (25%-50%) chance of micro-metastatic disease at presentation.

16 Does the radiation add anything, as XRT outcomes are similar to TURBT outcomes? Trimodality Therapy SeriesTreatment 5 yr survival 5 yr survival with bladder TURBT, XRT and concurrent Chemotherapy. Dunst (n=79)TURBT, cisplatin, XRT52%41% RTOG 1993 (n=42)Cisplatin and XRT52%42% Kachnic (n=106)TURBT, MCV and XRT52%43% RTOG 1997 (n=123)TURBT, MCV and XRT49%38% TURBT and Chemotherapy alone Given (n=93)TURBT and MCV51%18% Srougi (n=30)Partial C and MVAC53%20% It appears that concurrent chemo/XRT does add something.

17 Shipley- Massachusetts General Protocol Hydronephrosis, Poor renal function Irritable bladder, Low Capacity T4a/4b, CIS If yes, For surgery Radical Cystectomy If no, Maximal TURBT No Significant Tumour Remaining Bulky Tumour Remaining Chemo/ XRT Protocol-Induction CE 4 weeks after induction CR, consolidation Chemoradiation Residual Cancer

18 MGH- Chemoradiation Protocol Induction 2 cycles of neoadjuvant MCV –Methotrexate, cisplatin, vinblastine Concurrent cisplatin and 40Gy XRT Consolidation chemoradiation Further 24Gy XRT Cisplatin based chemotherapy

19 MGH- Results Patients selected for Trimodality therapy (n=190) –Denominator unknown Induction chemotherapy –29 (15%) had residual disease > RC –40 (21%) unable to tolerate ChemoRad > RC 121 (64%) went on to have consolidation Chemoradiation. After 4 years median FU –86 (45%) alive with NED –110 (58%) still had a bladder. Overall 5 yrs 54%

20 RTOG bladder sparing protocols All tumours are small. All tumours are able to be maximally resected. These are not the same tumours in cystectomy series.These are not the same tumours in cystectomy series. All patients are healthy with good ECOG status All patients were eligible for cystectomy.

21 Clinical Preictors of Outcome Stage (cT2=62%, cT3=47%) Hydronephrosis (CR= 37% vs 68%) CR on induction chemoradiation Quality of Life Cystectomy for bladder contracture (2-7%) On going urinary symptoms Women-19% incontinence Reduced urinary compliance in 22% Bowel symptoms- 22% Sexual dysfunction

22 Concerns with Bladder sparing therapy Need for complete TURBT (visibly clear) –CR 77% vs 54% for visble and not visible complete resection. –Survival 52% vs 5 yrs Urothelial cancer change –Those with CR to trimodality will develop –20-30% new or recurrent bladder tumor –Occur median of 2.1 years and mainly CIS –Ultimately 1/3 of recurrence need late cystectomy. Pelvic recurrence –12% Delay in cystectomy Limited diversion alternatives.

23 Is Bladder Preservation Equivalent to Radical Cystectomy? No but! Viable alternative for Pts wanting to preserve bladder Only small likely decrease in survival But Not all patients are suitable 50% will ultimately have cystectomy –Diversion choices will be limited. –Operation more difficult and complications higher. Not evidence that quality of life is actually better. A number of pts will have significant bladder and bowel symptoms.

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